Emerging studies based on the functional and structural imaging of the whole human brain have proposed a brain organization model in which there are highly and non-highly connected nodes. Nevertheless, the detailed analysis of the synapses is crucial to better understand the human brain organization.Here, we have performed detailed three-dimensional ultrastructural analyses in some highly connected (Brodmann areas 21, 24 and ventral and dorsal portions of 38) and non-highly connected (Brodmann areas 3b, 4 and 17) brain regions from human control autopsies with short-postmortem delay. Using three-dimensional electron microscopy (focused ion beam/ scanning electron microscopy), we have analyzed true synaptic contacts in layer III.Our results showed the highest number of synapses per volume in the dorsal portion of area 38 and the lowest in area 4, whereas the other areas showed similar values. Besides, all areas showed similar proportion of asymmetric (excitatory)/symmetric (inhibitory) synapses, and macular-shaped (learning) and complex-shaped (memory) synapses. Moreover, other synaptic parameters showed some common/specific characteristics depending on the region analyzed. For example, the synaptic size showed low values in the dorsal portion of area 38, and the proportion of synapses established on spines was particularly low in area 4.Thus, the present data indicate that the synaptic organization have some common or specific characteristics depending on the region analyzed, regardless of whether they are considered to be highly or non-highly connected regions.Figure: Number, type, size, shape and postsynaptic target distribution of synapses in layer III of different regions of the human cerebral cortex